Effects of denervation on the composition and synthesis of sarcolemmal proteins

In vitro synthesis of proteins and changes in polypeptide composition of sarcolemma were studied in innervated and denervated extensor digitorum longus muscle of the rat. A technique of evacuating myoplasm from muscle slices was used as a preliminary step in the preparation of three membrane fractions, M, H and S, containing sarcolemma. On the basis of findings from the previous study and the present investigation, it was concluded that the M fraction was most enriched with extrajunctional sarcolemma. In vitro incorporation of [3H]leucine into membrane proteins of the M fraction showed an apparent linear increase in the rate of protein synthesis from 1-10 days after denervation. The relative increase at 10 days was 137% greater than that of innervated controls. Fractions H and S showed a smaller relative increase. Polypeptide composition of M, H and S fractions based on SDS gel electrophoresis of innervated and denervated muscle, showed qualitative and quantitative changes. The most striking difference was a nominal 29 000 component in M that constituted a disproportionately large peak. Following 10 days of denervation the M fraction underwent significant compositional changes in its electrophoretic profile, the most dramatic of which was a large reduction in the proportion of the 19 000 component. The denervation-induced compositional change is discussed in light of known alterations in the chloride conductance of the muscle plasmalemma.